bardoxolone   Click here for help

GtoPdb Ligand ID: 2717

Synonyms: CDDO | RTA-401
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Bardoxolone was a Phase 3 NF-κB signaling inhibitor [2]. Although the recommended INN for this compound is bardoxolone, it is administered as bardoxolone methyl which has ChEMBL ID CHEMBL1762621. Bardoxolone can be described as a KEAP1 antagonist, as it antigonises KEAP1 interaction with the Nrf2 transription factor [1]. As this action releases Nrf2 from the inhibitory effect of the protein-protein interaction, it can also be described as a functional Nrf2 activator.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 95.23
Molecular weight 491.3
XLogP 6.3
No. Lipinski's rules broken 1
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Canonical SMILES N#CC1=CC2(C)C(C(C1=O)(C)C)CCC1(C2=CC(=O)C2C1(C)CCC1(C2CC(C)(C)CC1)C(=O)O)C
Isomeric SMILES N#CC1=C[C@@]2(C)[C@H](C(C1=O)(C)C)CC[C@@]1(C2=CC(=O)[C@H]2[C@@]1(C)CC[C@@]1([C@H]2CC(C)(C)CC1)C(=O)O)C
InChI InChI=1S/C31H41NO4/c1-26(2)10-12-31(25(35)36)13-11-30(7)23(19(31)16-26)20(33)14-22-28(5)15-18(17-32)24(34)27(3,4)21(28)8-9-29(22,30)6/h14-15,19,21,23H,8-13,16H2,1-7H3,(H,35,36)/t19-,21-,23-,28-,29+,30+,31-/m0/s1
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Summary of Clinical Use Click here for help
Clinical trials for treatment of chronic kidney disease (CKD) as a result of type 2 diabetes mellitus have been terminated. Visit to view currently registered drug trials involving this compound.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Bardoxolone inhibits the ubiquitinisation activity of KEAP1, a protein which interacts with and ubiquitinises the Nrf2 transcription factor (NFE2L2, Q16236) and sequesters Nrf2 to the cytoplasm. Bardoxolone-induced activation of Nrf2 leads to activation of Keap1-Nrf2 pathway which regulates genes (containing antioxidant response elements (AREs)) involved in antioxidant and anti-inflammatory responses [2-3,5].